Pro-resolving lipid mediator reduces amyloid-β42-induced gene expression in human monocyte-derived microglia

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外文摘要：Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain,suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology.Therefore,it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β.With this objective,we analyzed the relevance of human monocyte-derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42-induced Alzheimer's disease-like inflammation.Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease-like neuroinflammation in human brain microglia after incubation with amyloid-β42.Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia,protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part.We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1.In conclusion,monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients.Maresin 1 ameliorates amyloid-β42-induced changes in several genes of importance in Alzheimer's disease,highlighting its potential as a therapeutic target for Alzheimer's disease.

外文关键词：

Alzheimer's diseaseamyloid-βmaresinmicrogliamonocyteneuroinflammationresolutionRNA-sequencingspecialized pro-resolving lipid mediator

作者：

Ying Wang、Xiang Zhang、Henrik Biverstål、Nicolas G.Bazan、Shuai Tan、Nailin Li、Makiko Ohshima、Marianne Schultzberg、Xiaofei Li

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作者单位：

Department of Neurobiology,Care Sciences & Society,Division of Neurogeriatrics,Karolinska Institutet,Stockholm,Sweden

Department of Neurology,Neuroscience Center,The First Hospital of Jilin University,Changchun,Jilin Province,China

Department of Physiology and Pharmacology,Karolinska Institutet,Stockholm,Sweden

Department of Biosciences and Nutrition,Karolinska Institutet,Huddinge,Sweden

Neuroscience Center of Excellence,Louisiana State University,New Orleans,LA,USA

Department of Medicine,Solna,Clinical Pharmacology Group,Karolinska University Hospital,Stockholm,Sweden

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-01688

中国神经再生研究(英文版)

中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902

ISSN：1673-5374

年,卷(期)：2025.20(3)